FBI agent Sarah Ashburn is an expert investigator in New York City. She is disliked by other agents for her uptight and arrogant personality. Her supervisor, who is considering her for promotion, assigns her to a mission in Boston. She meets Boston Police Department detective Shannon Mullins, who is skilled but loudmouthed and hot-headed. The two women’s professional styles clash horribly during their attempt to interrogate a local drug dealer. Ashburn reluctantly agrees to work with Mullins.
Ashburn and Mullins tail a local nightclub manager to his business, Club Ekko, and place a bug on his phone to get information on a drug lord named Simon Larkin. Leaving the club, Ashburn and Mullins are confronted by DEA agents Craig and Adam, who’ve been working the Larkin case for months. The women discover a surveillance video in the DEA agents’ van showing that Mullins’ brother, Jason, recently released from prison where Mullins had sent him, appears to be connected to Larkin.
Ashburn convinces Mullins to go to her parents’ home to ask Jason for information on Larkin. The whole family are angry with Mullins for arresting her brother. But Jason tips Mullins off about the body of a murdered drug dealer, and chemicals on the victim’s shoes lead the women to an abandoned paint factory, where they witness a drug dealer being murdered by Julian Vincent, second-in-command of Larkin’s organization. They apprehend Julian but get no information on Larkin’s whereabouts, despite Mullins threatening to shoot Julian’s genitals.
The women spend the evening bonding in a bar. A drunk Ashburn reveals that her foster child past is to blame for her bad attitude. The next morning Ashburn discovers that she has given her car away to one of the bar patrons, but when he starts the car, it explodes.
Julian has escaped from custody and intends to harm Mullins’ family, so Mullins moves them into a motel. Jason tries to join the Larkin organization in an attempt to help Mullins solve the case. He gives her a tip about a drug shipment coming in, and despite Mullins’ reluctance, Ashburn calls in the FBI, who discover that it is only a pleasure cruise ship. Larkin shoots Jason for informing the FBI about the supposed drug shipment. Jason is rendered comatose. Mullins and Ashburn fall out, with Mullins vowing to bring her brother’s attacker to justice. They reconcile after arresting several drug dealers as they try to ascertain Larkin’s whereabouts.
The women equip themselves with assault weapons from Mullins’ extensive personal arsenal, and infiltrate one of Larkin’s warehouses, but they are captured and bound. Julian is about to torture them with knives when he gets called away by Larkin. Before Julian leaves, he stabs Ashburn in the leg and leaves the knife in the wound. Mullins removes the knife from Ashburn’s leg and uses it to cut the rope binding her hands. However, they are discovered by Craig and Adam. Craig begins to untie the two women, but as they realise Adam is Larkin, Adam shoots Craig before he draws his gun. Adam/Larkin has been working his own case from inside the DEA for several months.
Julian returns and Larkin orders him to kill Ashburn and Mullins while he goes to the hospital to kill Jason. Mullins has put her arms behind her chair so she looks tied up. After Larkin leaves, Mullins frees herself, grabs the knife in Ashburn’s leg and attacks him first. Ashburn throws herself to the floor whilst tied to her chair and he falls. Julian then grabs Ashburn’s round the throat and threatens to slit her throat as Mullins raises a gun. Ashburn head butts Julian backwards and incapacitates him. The duo race to the hospital to save Jason.
Upon their arrival, Mullins searches for Jason; Ashburn, hindered by the stab wound in her leg, lags behind. Mullins finds Jason’s room, but is disarmed by Larkin, who is about to kill Jason. Ashburn appears and subdues Larkin by shooting him in the genitals. Ashburn requests to stay in the FBI’s Boston field office, having developed a strong friendship with Mullins.
Jason is shown having fully recovered from his coma. Mullins receives a commendation from the Boston Police Department. Members of her family are present, and they all cheer for her.
The film ends with Mullins having signed the back of Ashburn’s yearbook, “Foster kid, now you have a sister”.